The overall objective of this SBIR project is the development of a rapid, high resolution optical method for in vivo imaging with a specific emphasis on intravascular imaging and the identification of vulnerable plaque. The approach uses a novel harmonic detection method for optical coherence tomography (OCT) that will allow depth resolved near infrared spectroscopy in conjunction with structural imaging. Since different structures in atherosclerotic plaques, such as the fibrotic caps, lipid pools and calcifications have different near infrared spectroscopic features, spectroscopic OCT is a promising approach to enhancing contrast in optical coherence tomography. [unreadable] Southwest Sciences recently developed a harmonic detection method for optical coherence tomography for the removal of artifacts inherent to Fourier domain OCT, but the method can also be used to provide the phase information necessary for spectroscopic OCT. Harmonic detection is easily applied because it uses a simple sine- wave modulation of the interferometer, with detection at harmonics of the applied wave. [unreadable] Phase I of this project focuses on demonstrating spectroscopic OCT using our harmonic detection technology. In particular, a near infrared absorption feature of lipid, which is an important component of vulnerable atherosclerotic plaques, will be used to demonstrate contrast enhancement resulting from spectroscopic OCT. In Phase II, we will proceed with design and construction of a fiber-optic, catheter probe instrument for intra-luminal imaging of arteries, with the goal of conducting Phase III clinical studies. [unreadable] [unreadable] [unreadable]